In recent years, increases in age-related diseases such as osteoporosis and dementia have become a serious social issue associated with aging. Various drugs have been developed to prevent or cure these age-related diseases. However, side effects of such drugs always need to be taken into consideration. Recently, attempts have been made to prevent or cure age-related diseases through a reconsideration of dietary habits or ingestion of a specific food ingredient. For example, ingestion of a basic protein in bovine milk is known to prevent or cure osteoporosis. Furthermore, a preventive and therapeutic agent against Alzheimer's defects of memory, containing sphingomyelin, a relatively abundant phospholipid in bovine milk, as an active ingredient is known.
An example of the age-related symptoms includes dulling of peripheral sensations, which is caused by not only aging, but also diseases such as diabetes. The dulling of peripheral sensations may lead to troubles, for example, a higher risk of suffering burns caused by failure to feel hot rightly on touching a hot object, or a risk of delaying the discovery of an injury caused by a dull sensation of pain. In recent years, studies that reduce dulling of peripheral sensations caused by aging or diseases have been conducted in order to prevent such risks. For example, it has been reported that exogenous ceramide and the enzymes sphingomyelinase and phosphatidylcholine-specific phospholipase C, the enzymes increase biosynthesis of endogenous ceramide, promote morphological differentiation of P-12 cells being neural model cells through 3T3 cells being an established fibroblast cell line, that is, a neurotrophic factor secreted by 3T3 cells (Non Patent Document 1). The promotion of morphological differentiation of the neural model cells indicates the effect of improving dulling of peripheral sensations. However, use of the above ceramide and enzymes, which are not food ingredients, requires examination of their safety. In such situations, there is a need for a safer agent that can improve dulled peripheral sensations through daily ingestion or application to the skin.
Components in milk are known to have many physiological activities. For example, milk-derived sphingomyelin and phospholipids are known to have an effect of improving dulling of peripheral sensations (Patent Document 1 and Patent Document 2). However, the effect of milk-derived proteins on improvements in dulling of peripheral sensations is not yet known. Examples of the milk-derived proteins include lactoperoxidase, lactoferrin, cystatin, and angiogenin.
Lactoperoxidase, present in milk, is a heme iron-containing glycoprotein, while details on its structure are yet to be known. Lactoperoxidase has been found to have an effect of inhibiting in vivo production of lipid peroxides and is used as an anti-aging agent that prevents loss of sight and motor skills, and decline in immune functions and the like, and a liver function improvement agent. Also, the glycoprotein is known to be used as a low-cariogenic nutrient composition due to its low cariogenicity. However, it is yet to be known that lactoperoxidase and an enzymatic hydrolysate therefrom produced with a protease have an effect of improving dulling of peripheral nerves, and are of use as a sensation-improving agent.
Lactoferrin and its hydrolysate are known to have an effect of preventing adhesion of pathogens to cells and an antiviral action. Moreover, the mixture with an epidermal growth factor is reported to increase a skin cell activating effect of the epidermal growth factor alone. Also, lactoferrin is generally known to have an effect of alleviating stress associated with pain and emotional stress. However, it is yet to be known that lactoferrin and an enzymatic hydrolysate therefrom produced with a protease have an effect of improving dulling of peripheral nerves, and are of use as a sensation-improving agent.
Cystatin is a cysteine protease inhibitor that inhibits the proteolytic activity of a cysteine protease having a SH group in the active center, and is found in animal tissues, cells, blood and urine. Also, cystatin's effect of inhibiting virus growth is found to be a beneficial effect. However, it is yet to be known that cystatin and an enzymatic hydrolysate therefrom produced with a protease have an effect of reducing dulling of peripheral nerves, and are of use as a sensation-improving agent.
Angiogenin is one of angiogenesis factors. Human angiogenin is known to be a protein having a molecular weight of 14,400, and is present in blood and milk. Bovine angiogenin is isolated from bovine milk and is subjected to amino acid sequencing, and the results have already been reported. A production of angiogenin from bovine milk by subjecting milk to cation exchange chromatography to apply the milk on the cation exchange column, eluting the adsorbate with an alkali metal salt solution of a weak organic acid, and subjecting the resulting eluate to cation exchange chromatography again and gel filtration chromatography to collect angiogenin is disclosed. Moreover, angiogenin is found to specifically inhibit melanin production in melanoma B-16 cells, and is reported to be used also as a possible whitening agent. However, it is yet to be known that angiogenin and an enzymatic hydrolysate therefrom produced with a protease have an effect of improving dulling of peripheral nerves, and are of use as a sensation-improving agent.